| Objective:①Using andrographolide as the principal agent, Eudragit S100 as the coating material, to prepare a kind of pH dependent form colon targeting pellet.②To establish the mass detection system for andrographolide, using high efficiency liquid chromatography to detect the dissolution of the drug in artificial intestinal juice and the content in the colon targeting pellet.③To investigate the delivery efficiency of andrographolide colon targeting pellet in vitro, and to study the influence of the delivery determination condition to the medicine release.④To set up a qualitation identification method for andrographolide colon targeting pellet, and to inspect the stability of the pellet in the influential factor test.Method:①Using lactose80 and MCC (102) as the bulking agent, applying the powder direct compression to prepare the pellet core. To Screen the prescription of the pellet core and the coating technology by single factor analysis, basing on the single factor tests, using orthogonal design test to optimize the prescription of the coating solution. According to the optimized preparation condition, trial-manufacture the andrographolide colon targeting coating pellet.②To establish the standard curve of andrographolide both in the dissolution medium and in the preparation by high efficiency liquid chromatography, and to authenticate the technology.③Using the similarity f2 factor of the stripping curve to evaluate the resemblance of different release curves, thus to definite the determination condition of the delivery rate.④Make use of physical and chemical methods and plate chromatography technology to identify andrographolide, to inspect the changes of appearance, contents and delivery rate of andrographolide colon targeting pellet in high temperature, high humidity and highlight. Results:①The optimal preparation technologies are that lactose80 and MCC (102) as the bulking agent, the ratio is 2:1; using Gum Arabic (3%) as the glidant. Using powder direct compression to prepare a kind of core pellet which the tablet hardness is 8～9 and the weight is 200mg. To fix the rate of rotation as 25 rpm, the angle of inclination is 45°, the entering wind temperature is 40～50℃, the puffing speed of the coating solution is 2.5mL/min, using Eudragit S100 as the coating material, diethyl phthalate as the elasticizer, and the account of elasticizer occupied 30% in the polymer, the increment of weight after coating is 6% in the end.②Using high efficiency liquid chromatography to determine the contents of andrographolide in dissolution medium, the equations is:y=62340x+46026, the linear correlation is good in 2.06-51.50μg/mL (r=0.9995), the precision is good too(RSD=0.89%), the average recovery is 98.3%; the equations of the andrographolide preparation is:y=64104x+36335; the linear correlation is good in 4～80μg/mL (r=0.9995), the precision is good too(RSD=0.59%), the average recovery is 98.92%.③The condition of delivery rate is that the rate of rotation is 75rpm using propeller, the coated tablets do not need heat treatment.Conclusion:①The prepared colon targeting pellet which using Eudragit S100 as the coating material is of high dependent with the pH, it can keep the drug not release in the stomach and small intestine, but release in the colon part. The delivery rate can consist with the experiment design.②The determination method by high efficiency liquid chromatography is accurate and reproductive, and it can be used as an approach of technology preference and quality control of andrographolide colon targeting pellet.③The physical and chemical methods for andrographolide qualitation identify is simple and operated, the separation effect by plate chromatography is good and specific; the colon pellet is quite stable in influencing factor test. |
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